Iron, Folate and Vitamin B12 Status of Apparently Healthy Irish Adult Women Attending General Practitioners in Inner-city Dublin

There is substantial related morbidity and mortality among men and women in developed countries. Certain events during the course of a woman’s life such as menstruation, pregnancy, lactation and the menopause may compromise haematinic nutrient status. The purpose of this study was to investigate iron, folate and vitamin B12 status among a sample of apparently healthy, non-pregnant Irish adult women attending general practitioners in inner-city Dublin. Dietary, socio-economic, medical and lifestyle factors contributing to status of these haematinic nutrients were extensively examined. The initial part of the work validated the methods in a representative sample of inner city Dublin women (n=35, mean age 40.3 years, SD 5.5 years). The Food Intake Questionnaire was developed and validated against the Diet History and biomarkers of haematinic nutrients in blood samples. An “Interview Questionnaire” was also developed and tested for reliability. The main study examined iron, folate, vitamin B12 and homocysteine levels in a sample of inner-city Dublin Woman (n=104, mean age 32.8 years, SD 11.2 years). Iron deficiency anaemia and low iron stores were discovered in 2.8% (n=3) and 14.4% (n=15) of the women respectively. Folate deficiency was found in 1.9% (n=2) of the female volunteers and a further 48% (n=50) had sub-optimal folate levels for women of childbearing age. Plasma vitamin B12 levels were all within the normal range. Plasma homocysteine levels were elevated in 12.5% (n=13) of the sample. Attitudes to nutrition and determinants of food choice were also assessed among the female volunteers (n=104, mean age 32.8 years, SD 11.2 years). Accuracy of self reported dietary perceptions with regard to adequacy of nutrient intakes and food consumption was examined. The relationship between self-reported physical activity level and BMI confirmed that leisure time physical activity is an important determinant of body weight. Body image concerns and slimming practices were assessed among female volunteers (n=134, mean age 34.7 years, SSD 10.7 years). Dissatisfaction with body weight was pervasive within the group at 82% (n=110). Many had used unsafe slimming practices such as smoking (30%, n=33) and diet pills (15%, n=16) in an attempt to lose weight. The results of this study highlight important nutritional issues for women in a primary healthcare setting

Adjusting for treatment switching in the METRIC study shows further improved overall survival with trametinib compared with chemotherapy

Trametinib, a selective inhibitor of mitogen-activated protein kinase kinase 1 (MEK1) and MEK2, significantly improves progression-free survival compared with chemotherapy in patients with BRAF V600E/K mutation–positive advanced or metastatic melanoma (MM). However, the pivotal clinical trial permitted randomized chemotherapy control group patients to switch to trametinib after disease progression, which confounded estimates of the overall survival (OS) advantage of trametinib. Our purpose was to estimate the switching-adjusted treatment effect of trametinib for OS and assess the suitability of each adjustment method in the primary efficacy population. Of the patients randomized to chemotherapy, 67.4% switched to trametinib. We applied the rank-preserving structural failure time model, inverse probability of censoring weights, and a two-stage accelerated failure time model to obtain estimates of the relative treatment effect adjusted for switching. The intent-to-treat (ITT) analysis estimated a 28% reduction in the hazard of death with trametinib treatment (hazard ratio [HR], 0.72; 95% CI, 0.52–0.98) for patients in the primary efficacy population (data cut May 20, 2013). Adjustment analyses deemed plausible provided OS HR point estimates ranging from 0.48 to 0.53. Similar reductions in the HR were estimated for the first-line metastatic subgroup. Treatment with trametinib, compared with chemotherapy, significantly reduced the risk of death and risk of disease progression in patients with BRAF V600E/K mutation–positive advanced melanoma or MM. Adjusting for switching resulted in lower HRs than those obtained from standard ITT analyses. However, CI are wide and results are sensitive to the assumptions associated with each adjustment method

How does reviewing the evidence change veterinary surgeons' beliefs regarding the treatment of ovine footrot? A quantitative and qualitative study

Footrot is a widespread, infectious cause of lameness in sheep, with major economic and welfare costs. The aims of this research were: (i) to quantify how veterinary surgeons’ beliefs regarding the efficacy of two treatments for footrot changed following a review of the evidence (ii) to obtain a consensus opinion following group discussions (iii) to capture complementary qualitative data to place their beliefs within a broader clinical context. Grounded in a Bayesian statistical framework, probabilistic elicitation (roulette method) was used to quantify the beliefs of eleven veterinary surgeons during two one-day workshops. There was considerable heterogeneity in veterinary surgeons’ beliefs before they listened to a review of the evidence. After hearing the evidence, seven participants quantifiably changed their beliefs. In particular, two participants who initially believed that foot trimming with topical oxytetracycline was the better treatment, changed to entirely favour systemic and topical oxytetracycline instead. The results suggest that a substantial amount of the variation in beliefs related to differences in veterinary surgeons’ knowledge of the evidence. Although considerable differences in opinion still remained after the evidence review, with several participants having non-overlapping 95% credible intervals, both groups did achieve a consensus opinion. Two key findings from the qualitative data were: (i) veterinary surgeons believed that farmers are unlikely to actively seek advice on lameness, suggesting a proactive veterinary approach is required (ii) more attention could be given to improving the way in which veterinary advice is delivered to farmers. In summary this study has: (i) demonstrated a practical method for probabilistically quantifying how veterinary surgeons’ beliefs change (ii) revealed that the evidence that currently exists is capable of changing veterinary opinion (iii) suggested that improved transfer of research knowledge into veterinary practice is needed (iv) identified some potential obstacles to the implementation of veterinary advice by farmers

Translating In Vivo Metabolomic Analysis of Succinate Dehydrogenase–Deficient Tumors Into Clinical Utility

Purpose Mutations in the mitochondrial enzyme succinate dehydrogenase (SDH) subunit genes are associated with a wide spectrum of tumors, including pheochromocytomas and paragangliomas, GI stromal tumors, renal cell carcinomas, and pituitary adenomas. SDH-related tumorigenesis is believed to be secondary to accumulation of the oncometabolite succinate. Our aim was to investigate the potential clinical applications of proton-1 magnetic resonance spectroscopy (1H-MRS) in a range of suspected SDH-related tumors. Patients and Methods Fifteen patients were recruited to this study. Respiratory-gated single-voxel 1H-MRS was performed at 3T to quantify the content of succinate at 2.4 ppm and choline at 3.22 ppm. Results A succinate peak was seen in six patients, all of whom had germ line SDHx mutations or loss of SDHB by immunohistochemistry. Succinate peaks were also detected in two patients with metastatic wild-type GI stromal tumors and no detectable germ line SDHx mutations but with somatic epimutations in SDHC. Three patients without tumor succinate peaks retained SDHB expression, consistent with SDH functionality. In six patients with borderline or absent peaks, technical difficulties such as motion artifact rendered 1H-MRS difficult to interpret. Sequential imaging in a patient with a metastatic abdominal paraganglioma demonstrated loss of the succinate peak after four cycles of [177Lu]DOTATATE, with a corresponding biochemical response in normetanephrine. Conclusion This study has demonstrated the translation into clinical practice of in vivo metabolomic analysis using 1H-MRS in patients with SDH-deficient tumors. Potential applications include noninvasive diagnosis and disease stratification, as well as monitoring of tumor response to targeted treatments. </jats:sec

Clinical and Molecular Features of Renal and Pheochromocytoma/Paraganglioma Tumor Association Syndrome (RAPTAS): Case Series and Literature Review.

CONTEXT: The co-occurrence of pheochromocytoma (PC) and renal tumors was linked to the inherited familial cancer syndrome von Hippel-Lindau (VHL) disease more than six decades ago. Subsequently, other shared genetic causes of predisposition to renal tumors and to PC, paraganglioma (PGL), or head and neck paraganglioma (HNPGL) have been described, but case series of non-VHL-related cases of renal tumor and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS) are rare. OBJECTIVE: To determine the clinical and molecular features of non-VHL RAPTAS by literature review and characterization of a case series. DESIGN: A review of the literature was performed and a retrospective study of referrals for investigation of genetic causes of RAPTAS. RESULTS: Literature review revealed evidence of an association, in addition to VHL disease, between germline mutations in SDHB, SDHC, SDHD, TMEM127, and MAX genes and RAPTAS [defined here as the co-occurrence of tumors from both classes (PC/PGL/HNPGL and renal tumors) in the same individual or in first-degree relatives]. In both the literature review and our case series of 22 probands with non-VHL RAPTAS, SDHB mutations were the most frequent cause of non-VHL RAPTAS. A genetic cause was identified in 36.3% (8/22) of kindreds. CONCLUSION: Renal tumors and PC/PGL/HNPGL tumors share common molecular features and their co-occurrence in an individual or family should prompt genetic investigations. We report a case of MAX-associated renal cell carcinoma and confirm the role of TMEM127 mutations with renal cell carcinoma predisposition

A hidden crisis: strengthening the evidence base on the current failures of rural groundwater supplies

New ambitious international goals for universal access to safe drinking water depend critically on the ability of development partners to accelerate and sustain access to groundwater. However, available evidence (albeit fragmented and methodologically unclear) indicates >30% of new groundwater-based supplies are non-functional within a few years of construction. Critically, in the absence of a significant systematic evidence base or analysis on supply failures, there is little opportunity to learn from past mistakes, to ensure more sustainable services can be developed in the future. This work presents a new and robust methodology for investigating the causes of non-functionality, developed by an interdisciplinary team as part of an UPGro catalyst grant. The approach was successfully piloted within a test study in NE Uganda, and forms a basis for future research to develop a statistically significant systematic evidence base to unravel the underlying causes of failure